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BMC of whole body and BMD of spine, total hip, and femoral neck - compare at different timepoints [ Time Frame: 96 weeks ]

For BMC of whole body and BMD of spine, total hip, and femoral neck, compare change from baseline to week 24, change from baseline to week 48, and change from baseline to week 96 by randomized study group, with analyses using measured BMC/BMD and Z-scores;

Measure change from baseline to week 48 and change from baseline to week 96 in Gluc homeostasis [ Time Frame: 96 weeks ]

To measure change from baseline to week 48 and change from baseline to week 96 in Gluc homeostasis (fasting insulin and Gluc and calculated HOMA-IR and their relationship to changes in 25-OHD, 1,25-OHD, and free 1,25-OHD index for the randomized study groups and for different attained vitamin D serum concentrations;

To compare 25-OHD serum concentrations by randomized study group at all-time points and change from baseline to week 48 and 96;

Compare the mean 25-OHD serum concentration and to measure the effect of concurrent treatment with EFV or ritonavir on serum 25-OHD concentrations and changes during the study [ Time Frame: 96 weeks ]

To compare the mean 25-OHD serum concentration by randomized study group and to measure the effect of concurrent treatment with EFV or ritonavir on serum 25-OHD concentrations and changes during the study;

To measure the relationship of 25-OHD, 1,25-OHD, and free 1, 25-OHD serum concentrations to baseline and change from baseline to week 24, baseline to week 48, and baseline to 96 in BMD/BMC, markers of Ca-PO4-FGF23 activity, markers of bone turnover, renal glomerular and tubular toxicity, and Gluc homeostasis

A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Effectiveness of Vitamin D3 50,000 IU Every 4 Weeks to Increase Bone Mineral Density and Decrease Tenofovir-Induced Hyperparathyroidism in Youth With HIV Infection Being Treated With Tenofovir-Containing Combination Antiretroviral Therapy

Brief Summary

This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days.

Detailed Description

This is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.

Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca.

DXA measurement of whole-body BMC, and BMD at spine and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-PO4 axis, PTH-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48 Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis.

Safety, measured by SCa and SCr, will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The ATN109 study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of the visit. Viral load and CD4 cell count results will be recorded for the ATN109 study at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations are not performed within the protocol specified timeframes they will be drawn at the time of the visit.

Subjects randomized to Group A will receive Vitamin D3 50,000 IU orally every four weeks by directly observed therapy (DOT). In addition all subjects receive a multivitamin (MVI) that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Calcium (Ca). Subjects will self-administer one MVI tablet orally once daily.

Intervention: Dietary Supplement: Vitamin D3 50,000 IU

Placebo Comparator: Group B: Vitamin D3 placebo

Subjects randomized to Group B will receive Vitamin D3 placebo orally every four weeks by DOT. In addition all subjects receive a MVI that contains ingredients not to exceed 600 IU of vitamin D3 and 200 mg of Ca. Subjects will self-administer one MVI tablet orally once daily.

HIV-1 infection as documented in subject's medical record by at least one of the following criteria:

reactive HIV screening test result with an antibody based FDA-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 Indirect Immunofluorescence, Antibody Differentiation Assay (Multispot)); or

positive HIV-1 DNA PCR assay; or

plasma HIV-1 quantitative RNA assay >1,000 copies/mL; or

positive plasma HIV-1 RNA qualitative assay

Subjects must have at least one documented HIV viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no HIV viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.

Currently being treated for at least 180 days by the time of randomization with a TDF containing cART with at least 2 other FDA approved ARVs (NOTE: This may include a TDF-containing fixed drug combination medication);

Willingness and ability to remain on the same cART regimen for the duration of study participation;

Willingness and ability to participate in the study, follow all study procedures for the duration of study participation, and provide written informed consent or assent with parental permission, if applicable; and

For females of child-bearing potential, agreement to use a minimum of one proven-effective method of birth control and willingness to postpone pregnancy for the duration of study participation (see section 5.3.2 for permitted hormonal contraceptives)

Exclusion Criteria:

To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization:

NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.